This Program-Project encompasses a broad fundamental approach to the chemistry, biochemistry, and biology of tumor initiation, promotion, and progression by chemicals. The program includes major studies on the activation of chemical carcinogens, the interactions of ultimate carcinogens with cellular macromolecules, biochemical events associated with the promotion of initiated cells to the development of gross tumors, factors that affect the differentiation of cells and the progression and regression of neoplastic or preneoplastic cells, and the biological and biochemical diversity of prenoplastic and neoplastic lesions. The program includes investigations at the subcellular level, in cell culture, and in the whole animal.